The potency of luliconazole against clinical and environmental Aspergillus nigri complex

2020 ◽  
Author(s):  
Sahar Hivary ◽  
Mahnaz Fatahinia ◽  
Marzieh Halvaeezadeh ◽  
Ali Zarei Mahmoudabadi
Keyword(s):  
Aspergillus Niger ◽  
Amphotericin B ◽  
Antifungal Susceptibility ◽  
Vitro Activity ◽  
Molecular Technique ◽  
In Vitro Activity ◽  
Environmental Isolates ◽  
Minimum Effective Concentration ◽  
Clinical Strains

Background and Objectives: Black Aspergillus strains including, Aspergillus niger and A. tubingensis, are the most cause of otomycosis with worldwide distribution. Although, amphotericin B was a Gold standard for the treatment of invasive fungal infection for several decades, it gradually replaced by fluconazole and /or voriconazole. Moreover, luliconazole, appears to offer the best potential for in vitro activity against black Aspergillus strains. The aim of the present study was to compare the in vitro activity luliconazole, with commonly used antifungals against clinical and environmental strains of black Aspergillus. Materials and Methods: Sixty seven (37 clinical and 30 environmental) strains of black Aspergillus were identified using morphological and molecular technique (β-Tubulin gene). In addition, antifungal susceptibility test was applied according to CLSI M38 A2. The results were reported as minimum inhibitory concentration (MIC) or minimum effective concentration (MEC) range, MIC50 or MEC50, MIC90 or MEC90 and MIC geometric (GM) or MECGM. Results: Aspergillus niger was the common isolate followed by, A. tubingensis in both clinical and environmental strains. The lowest MIC range, MIC50, MIC90, and MICGM was attributed to luliconazole in clinical strains. The highest resistant rate was found in amphotericin B for both clinical (86.5%) and environmental (96.7%) strains whereas 54.1% of clinical and 30% of environmental isolates were resistant to caspofungin. Clinical strains of Aspergillus were more sensitive to voriconazole (86.7%) than environmental strains (70.3%). On the other hand, 83.8% of clinical and 70% of environmental isolates were resistant to posaconazole. Conclusion: Luliconazole versus amphotericin B, voriconazole, posaconazole and caspofungin is a potent antifungal for Aspergillus Nigri complex. The in vitro extremely antifungal efficacy against black Aspergillus strains of luliconazole, is different from those of other used antifungals.

In vitro activity of olorofim against clinical isolates of Scedosporium species and Lomentospora prolificans using EUCAST and CLSI methodologies

2020 ◽  
Vol 75 (12) ◽  
pp. 3582-3585
Author(s):  
Olga Rivero-Menendez ◽  
Manuel Cuenca-Estrella ◽  
Ana Alastruey-Izquierdo
Keyword(s):  
Amphotericin B ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Scedosporium Apiospermum ◽  
In Vitro Activity ◽  
Scedosporium Dehoogii ◽  
Scedosporium Species

Abstract Objectives To evaluate the in vitro activity of olorofim, a new broad-spectrum antifungal with a novel mechanism of action, against a collection of 123 Spanish clinical isolates belonging to five Scedosporium species and Lomentospora prolificans. Methods The activity of olorofim against Scedosporium apiospermum (n = 30), Scedosporium boydii (n = 30), Scedosporium ellipsoideum (n = 10), Scedosporium aurantiacum (n = 20), Scedosporium dehoogii (n = 3) and Lomentospora prolificans (n = 30) was compared with that of amphotericin B, voriconazole, isavuconazole and micafungin by performing EUCAST and CLSI reference methods for antifungal susceptibility testing. Results Amphotericin B and isavuconazole showed MICs ≥2 mg/L for all the species evaluated and voriconazole was moderately active (GM, MIC50 and MIC90 values ≤2 mg/L) against all of them except L. prolificans. Micafungin was effective against S. apiospermum complex strains, but exhibited elevated MECs for S. dehoogii and S. aurantiacum. Olorofim showed low MICs for all the Scedosporium strains tested (GM values were lower than 0.130 and 0.339 by the EUCAST method and the CLSI method, respectively, for all of the species), including those belonging to the MDR species L. prolificans, for which GM values were 0.115 and 0.225 mg/L by the EUCAST method and the CLSI method, respectively, while the GMs for the rest of the antifungals evaluated were higher than 3.732 mg/L using both methodologies. Conclusions Olorofim displayed promising in vitro activity against the Scedosporium and L. prolificans strains tested, some of which have reduced susceptibility to the antifungals that are currently in use.

The high efficacy of luliconazole against environmental and otomycosis Aspergillus flavus strains

2020 ◽  
Author(s):  
Maryam Moslem ◽  
Ali Zarei Mahmoudabadi
Keyword(s):  
Amphotericin B ◽  
Aspergillus Flavus ◽  
Inhibitory Concentration ◽  
Topical Therapy ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Environmental Isolates ◽  
Strong Activity ◽  
Microscopic Features

Background and Objectives: Luliconazole is currently confirmed for the topical therapy of dermatophytosis. Moreover, it is found that luliconazole has in vitro activity against some molds and yeast species. The aim of the present study was to evaluate the efficacy of luliconazole in comparison to routine used antifungals on clinical and environmental isolates of Aspergillus flavus. Materials and Methods: Thirty eight isolates of A. flavus (18 environmental and 20 clinical isolates) were detected based on morphological and microscopic features and also PCR-sequencing of β-tubulin ribosomal DNA gene. All the isolates were tested against luliconazole, voriconazole, amphotericin B and caspofungin. Minimum inhibitory concentration (MIC),   90   MIC50, MIC isolates.   and MIC Geometric (GM) were calculated using CLSI M38-A2 protocol for both environmental and clinical   GM   Results: Luliconazole with extremely low MIC range, 0.00049-0.00781 μg/mL and MIC   0.00288 μg/mL showed very   strong activity against both clinical and environmental A. flavus isolates. Moreover, voriconazole inhibited 100% of isolates at defined epidemiological cutoff values (ECV ≤ 2 µg/ml). 50% and 27.8% of clinical and environmental isolates of A. flavus, were resistant to caspofungin, respectively. Whereas, all the isolates were found to be resistant to amphotericin B.   GM   Conclusion: The analysis of our data clearly indicated that luliconazole (with MIC   0.00244 µg/ml for clinical and 0.00336   μg/ml for environmental isolates) had the highest in vitro activity against A. flavus strains.

scholarly journals Luliconazole, a New Antifungal, vs Amphotericin B, Voriconazole, Posaconazole and Caspofungin against Clinical and EnvironmentalAspergillusNigri Complex

2019 ◽  
Author(s):  
Sahar Hivary ◽  
Mahnaz Fatahinia ◽  
Marzieh Halvaeezadeh ◽  
Ali Zarei Mahmoudabadi
Keyword(s):  
Amphotericin B ◽  
Gold Standard ◽  
Antifungal Susceptibility ◽  
Environmental Isolates ◽  
Clinical Strains ◽  
Molecular Tests ◽  
Black Aspergilli ◽  
Antifungal Susceptibility Test ◽  
The Common

ABSTRACTBlack Aspergilli are,the most causes of aspergillosis andAspergillus niger and A. tubingensis are two more frequently isolates. Although, amphotericin B was a gold standard for the treatment of invasive fungal infection for several decades, it replaced by several new antifungals. Furthermore, a novel antifungal, luliconazole, appears to offer the potential for improved therapy for aspergillosis. The aim of the present study was to compare the effect of a novel antifungal agent, luliconazole, with classical antifungalagainst clinical and environmental strains of black Aspergilli. Sixty seven strains of black Aspergilli were identified using morphological and molecular tests (β-Tubulin gene). Antifungal susceptibility test was applied according to CLSI M38 A2. The results were reported as MIC range, MIC50, MIC90and MICGM. In the present study,A. nigerwas the common isolate followed by,A. tubingensisand 54.1% (clinical) and 30% (environmental) of isolates were resistant to caspofungin. The highest resistant rate was found in amphotericin B for both clinical (86.5%) and environmental (96.7%) strains. Clinical strains ofAspergilluswere more sensitive to voriconazole (86.7%) than environmental strains (70.3%). On the other hand, 83.8% of clinical and 70% of environmental isolates were resistant to posaconazole, respectively. It is found that the lowest MIC range, MIC50, MIC90, and MICGMwas attributed to luliconazole in clinical strains. In conclusion, luliconazole vs. routine antifungal is a potent antifungal forA. nigercomplexin vitro. The MIC range, MIC50, MIC90and MICGMof luliconazole against black Aspergilli were the lowest among the representative tested antifungals.

scholarly journals 1282. Manogepix, the Active Moiety of the Investigational Agent Fosmanogepix, Demonstrates In vitro Activity Against Members of the Fusarium oxysporum and Fusarium solani Species Complexes

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S656-S656
Author(s):  
Hamid Badali ◽  
Hoja Patterson ◽  
Carmita Sanders ◽  
Barbara Mermella ◽  
Connie Gibas ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Susceptibility ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Research Support ◽  
Inhibition Of Growth ◽  
Active Moiety ◽  
Species Complexes

Abstract Background Invasive fusariosis is associated with marked morbidity and mortality in immunocompromised hosts, and treatment options are limited. Common etiologic agents include members of the F. oxysporum and F. solani species complexes (FOSC and FSSC, respectively). Manogepix (MGX), the active moiety of fosmanogepix, is a novel GWT1 inhibitor with broad antifungal activity. Fosmanogepix has previously shown in vivo efficacy in an immunocompromised murine model of invasive fusariosis. Our objective was to evaluate the in vitro activity of MGX against FOSC and FSSC isolates. Methods Clinical isolates of FOSC (n=49) and FSSC (19) were identified by combined phenotypic characteristics and DNA sequence analysis of the translation elongation factor 1-alpha (TEF1α) and RNA polymerase II second largest subunit (RPB2). Antifungal susceptibility testing was performed by CLSI M38 broth microdilution. Minimum effective concentrations (MEC) and minimum inhibitory concentrations (MIC) were read after 48 hours of incubation at 50% and 100% inhibition of growth for MGX, and MIC values were read for amphotericin B, posaconazole, isavuconazole, and voriconazole at 100% inhibition of growth. Results MGX demonstrated potent in vitro activity against both FOSC and FSSC isolates. Against the 49 FOSC isolates, the MGX MECs ranged from <0.015-0.03 mg/mL, and MICs at the 50% inhibition of growth endpoint ranged from <0.015-0.12 mg/mL (Table). MIC values were higher when read at 100% inhibition of growth. Similar results were observed against FSSC isolates (MEC and MIC ranges <0.015 and <0.015-0.25 mg/mL, respectively). MGX MEC and MIC 50% inhibition values were in close agreement for both FOSC and FSSC isolates. Of the other antifungals tested, amphotericin B demonstrated in vitro good activity (MIC ranges 1-4 and 0.25-4 mg/mL against FOSC and FSSC, respectively). In contrast, the azoles demonstrated reduced susceptibility (MIC range 1- >16 mg/mL). MIC/MEC values (mcg/mL) for manogepix and other antifungals against FOSC and FSSC isolates Conclusion MGX demonstrated in vitro activity against FOSC and FSSC clinical isolates. Both changes in fungal morphology (MEC) and reductions in growth (MIC 50% inhibition) were observed. Clinical studies are ongoing to determine the efficacy of fosmanogepix in patients with invasive fungal infections. Disclosures Ashraf S. Ibrahim, PhD, Astellas Pharma (Research Grant or Support) Karen J. Shaw, PhD, Amplyx (Consultant)Forge Therapeutics (Consultant) Nathan P. Wiederhold, PharmD, Astellas (Grant/Research Support)BioMerieux (Grant/Research Support)Cepheid (Grant/Research Support)Covance (Grant/Research Support)F2G (Grant/Research Support)Gilead (Speaker’s Bureau)Mayne Pharma (Advisor or Review Panel member)Sfunga (Grant/Research Support)

scholarly journals In Vitro Activity of Ravuconazole against 923 Clinical Isolates of Nondermatophyte Filamentous Fungi

2005 ◽  
Vol 49 (12) ◽  
pp. 5136-5138 ◽  
Author(s):  
Manuel Cuenca-Estrella ◽  
Alicia Gomez-Lopez ◽  
Emilia Mellado ◽  
Guillermo Garcia-Effron ◽  
Araceli Monzon ◽  
...  
Keyword(s):  
Filamentous Fungi ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Clinical Strains ◽  
Scedosporium Prolificans

ABSTRACT The in vitro activities of ravuconazole against 575 clinical strains of Aspergillus spp. and 348 nondermatophyte non-Aspergillus spp. were analyzed. Ravuconazole was active against Aspergillus spp., other hyaline filamentous fungi, black molds, and some Mucorales. Species such as Scedosporium prolificans, Fusarium spp., and Scopulariopsis spp. were resistant to the triazole.

scholarly journals In Vitro Activity of Nystatin Compared with Those of Liposomal Nystatin, Amphotericin B, and Fluconazole against Clinical Candida Isolates

2002 ◽  
Vol 40 (4) ◽  
pp. 1406-1412 ◽  
Author(s):  
S. Arikan ◽  
L. Ostrosky-Zeichner ◽  
M. Lozano-Chiu ◽  
V. Paetznick ◽  
D. Gordon ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Vitro Activity ◽  
In Vitro Activity

In vitro activity of voriconazole, itraconazole, caspofungin, anidulafungin (VER002, LY303366) and amphotericin B against aspergillus spp

2003 ◽  
Vol 45 (2) ◽  
pp. 131-135 ◽  
Author(s):  
María del Carmen Serrano ◽  
Anastasio Valverde-Conde ◽  
M.ónica Chávez ◽  
Samuel Bernal ◽  
Rosa María Claro ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Vitro Activity ◽  
In Vitro Activity

scholarly journals Comparison of In Vitro Activity of Liposomal Nystatin againstAspergillus Species with Those of Nystatin, Amphotericin B (AB) Deoxycholate, AB Colloidal Dispersion, Liposomal AB, AB Lipid Complex, and Itraconazole

1999 ◽  
Vol 43 (5) ◽  
pp. 1264-1266 ◽  
Author(s):  
Karen L. Oakley ◽  
Caroline B. Moore ◽  
David W. Denning
Keyword(s):  
Amphotericin B ◽  
Aspergillus Terreus ◽  
Antifungal Agents ◽  
Geometric Mean ◽  
Colloidal Dispersion ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Lipid Complex

ABSTRACT We compared the in vitro activity of liposomal nystatin (Nyotran) with those of other antifungal agents against 60Aspergillus isolates. Twelve isolates were itraconazole resistant. For all isolates, geometric mean (GM) MICs (micrograms per milliliter) were 2.30 for liposomal nystatin, 0.58 for itraconazole, 0.86 for amphotericin B (AB) deoxycholate, 9.51 for nystatin, 2.07 for liposomal AB, 2.57 for AB lipid complex, and 0.86 for AB colloidal dispersion. Aspergillus terreus (GM, 8.72 μg/ml; range, 8 to 16 μg/ml) was significantly less susceptible to all of the polyene drugs than all other species (P = 0.0001).

scholarly journals In vitro activity of a new echinocandin, LY303366, compared with those of amphotericin B and fluconazole against clinical yeast isolates.

1997 ◽  
Vol 41 (5) ◽  
pp. 1156-1157 ◽  
Author(s):  
O Uzun ◽  
S Kocagöz ◽  
Y Cetinkaya ◽  
S Arikan ◽  
S Unal
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method

The in vitro activity of LY303366, a new echinocandin derivative, was evaluated with 191 yeast isolates by a broth microdilution method. The MICs at which 50% of the isolates were inhibited were 0.125 microg/ml for Candida albicans and C. tropicalis, 0.25 microg/ml for C. krusei, C. kefyr, and C. glabrata, and 2.0 microg/ml for C. parapsilosis.

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